Some processes, such as cell culture, need that a fluid inside a container is agitated. This step can be achieved in many ways, but achieving it by introducing some moving external piece inside the container has many disadvantages.
Firstly, it is more difficult to ensure the watertightness of the container, as there must be an opening for the external piece to come in, and that opening must let the piece move. Furthermore, it is more difficult to ensure the sterility of the inner part of the container.
Different solutions have been proposed to achieve contained, non-intrusive agitation within closed vessels. These solutions can be grouped into three broad approaches:
Agitation of the Vessel.
U.S. Pat. No. 6,190,913 describes a rocking platform that applies a rocking movement to a bag partially filled with a cell suspension, thus achieving simultaneous agitation of the suspension and aeration of the culture due to gas exchange between the liquid phase and the gas phase on top.
U.S. Pat. No. 3,941,661 describes adherent cells growing on the inner wall of a cylindrical bottle which are periodically submerged in a liquid culture medium contained in the bottle as the horizontal bottle rotates about its longitudinal axis.
U.S. Pat. No. 5,816,702 proposes the use of a vane mounted in the interior of a drum thus increasing the mixing of the fluid contents of the vessel.
U.S. Pat. No. 4,732,487 describes the application of an oscillating movement to the wall of a vessel such that this movement transfers the oscillating movement to a mixing plate secured to the inner side of the oscillating wall. The plate oscillates at larger amplitude than that applied to the wall, thus producing a mixing effect of liquids contained in the vessel.
U.S. Pat. No. 4,685,811 describes the use of a fluidic diode comprising a perforated plate contained in a vessel in such a way that the different path followed by the liquid when flowing in different directions creates a mixing effect.
U.S. Pat. No. 7,083,323 proposes the movement from one compartment to another of the liquid content of a multi-compartment flexible vessel. By, compressing the walls of the different compartments, the liquid is forced to pass through small passages that increase flow speed and create a mixing effect.
Bubbling Gas
U.S. Pat. No. 5,443,985 proposes the culture of cells in suspension using a long inclined culture chamber where gas bubbles introduced at the bottom of the chamber progressed to the top of the chamber along the interphase between the cell suspension and the chamber wall, thus gently agitating the cell suspension contained in the chamber and simultaneously providing gas exchange.
Magnetic Agitation
Magnetic coupling is commonly used in open systems to agitate the liquid contents of vessels. In these systems an open vessel containing the liquid to be agitated and a magnet Is placed on top of a surface that covers a rotating magnetic field. Examples of this technique can be found in U.S. Pat. No. 4,209,259 or in U.S. Pat. No. 3,647,632.
Document U.S. Pat. No.3,290,017 A describes a partitioned container for storing a plurality of different ingredients that must be kept separated until ready for use. In one of the embodiments, fingers are used to push a ball-shaped barrier along the inside of a tube.
However, all of these existing systems have at least one of the following drawbacks: the agitation intensity, and therefore the shear forces, is poorly controlled, thus limiting the application to shear resistant contents; continuous fluid feeding and exhausting is not possible due to tubing entanglement, limiting automation; direct agitation occurs only in a reduced volume of the vessel content, reducing efficacy; liquid transfer from one vessel to another through small passages is required to achieve agitation, therefore limiting the size of solid structures in the interior of the vessel and increasing the size of the overall system ; the use of metallic components in the interior of the vessel prevents the use of some sterilizing technologies, what prevents the use of pre-sterilized vessels; and the agitating mechanism is large and complex, limiting its application in particularly controlled environments.
All of the afore-mentioned drawbacks are overcome by the disclosed invention.